Mass spectrometers are widely used to analyse ions on the basis of their mass-to-charge ratio (m/z). Mass spectrometry has become a primary technique for analysis of proteins. The development of electrospray ionization coupled to mass spectrometry has enabled the analysis of large intact proteins and protein complexes, even when the latter are held together by weak non-covalent interactions. A new field has thus emerged, termed native protein mass spectrometry, which focuses on analysis of such species at near-physiological conditions (i.e. at approximately neutral pH). Applications of this approach range from the detailed study of equilibria between different quaternary structures as influenced by environmental changes or binding of substrates or cofactors, to the analysis of intact nano-machineries, such as whole virus particles, proteasomes and ribosomes [A. Heck. Native mass spectrometry: a bridge between interactomics and structural biology, Nature Methods 5 (2008) 927-933].
Typically, ions produced at such conditions have a lower charge state and hence high m/z (normally exceeding m/z 5,000-10,000). This brings them outside of the typical mass range of most mass spectrometers and hence it has become a typical application for time-of-flight (TOF) mass analysers due to their ability to access very high m/z, frequently coupled with dedicated quadrupole mass filters (operating at very low frequencies to extend the mass range). However, due to problems with ion detection as secondary electron multiplication becomes ineffective at such m/z for typical ion energies, additional post-acceleration has had to be introduced. The use of TOF mass analysers, however, has drawbacks since the low duty cycle and transmission of typically used orthogonal-acceleration time-of-flight instruments limit sensitivity of detection while limited flight path and post-acceleration limit resolving power to less than one thousand. In order to improve analysis performance for large ions it has been proposed to use ion cooling at elevated pressures after the atmosphere-to-vacuum interface in Q-TOF instruments as described in I. V. Chernushevich, B. A. Thomson, “Collisional Cooling of Large Ions in Electrospray Mass Spectrometry”, Anal. Chem. 2004, 76, 1754-1760.
In view of the above background, the present invention has been made.